Application of HPLC mixed-mode chromatography in determining radiochemical purity of [14C] labeled metformin hydrochloride

Metformin is currently prescribed worldwide to treat type 2 diabetes, and therefore, radiolabeled [14C] metformin is often prepared for clinical comparisons of new drug candidates. Prior to using the radiolabeled metformin, the purity needs to be determined to ensure the quality of the material. While typical reversed‐phase LC methods are often the first choice for purity analysis, they are not suitable for this determination because the compound is poorly retained under these conditions. Mixed‐mode chromatography has been demonstrated to overcome these retention issues, and therefore, this methodology was utilized for the purity determination of radiolabeled metformin. A mixed‐mode chromatography method was developed for the purity assessment of [14C] metformin. The described robust method easily separated the polar impurity components, allowing for the accurate purity determinations of several batches.